Support is requested for a multidisciplinary study to delineate subtypes of affective disorders in terms of clinical, genetic, biochemical, and behavioral criteria. Recent reports support the classification of patients with affective disorders into at least two sub-groups, bipolar (Manic-Depressive), and unipolar (Depression only). We propose to establish extensive profiles of affectively ill patients and their relatives by assessing presence or absence of illness in relatives (by means of a structured interview), by studying possible linkage of the illness with the X chromosome (by testing for color blindness and Xg blood group) by determining the activity of red blood cell catechol-O-methyltransferase and other catecholamine metabolizing enzymes, and by assaying indoleamine and catecholamine metabolites in urine and in cerebrospinal fluid. The data from affected and non-affected relatives may be of value in detecting and clarifying biologic differences which may be genetically determined. These studies may also establish a classification of affective disorders based on genetic and biological criteria and define homogeneous populations for the diagnosis, treatment and prevention of these illnesses. The groupings of patients in this study are consistent with the classification used by other investigators; the biologic data obtained from the metabolic studies regarding these patients can complement investigations from other centers. Our facilities include an outpatient clinic for the clinical and genetic investigations and an 8-bed metabolic clinical research unit for more detailed studies.